chr5-31459328-T-A

Variant names:

• chr5-31459328-T-A
• rs640831
• NM_001382508.1:c.2574+4908A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001382508.1(DROSHA):​c.2574+4908A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 150,588 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00015 (1 hom., cov: 26)
• Consequence: DROSHA NM_001382508.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• Publications: 12 publications found

Genes affected

DROSHA (HGNC:17904): (drosha ribonuclease III) This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High AC in GnomAd4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	NM_001382508.1	MANE Select	c.2574+4908A>T		intron	N/A	NP_001369437.1
	DROSHA	NM_013235.5		c.2574+4908A>T		intron	N/A	NP_037367.3
	DROSHA	NM_001100412.2		c.2463+4908A>T		intron	N/A	NP_001093882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	ENST00000344624.8	TSL:5 MANE Select	c.2574+4908A>T		intron	N/A	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.2574+4908A>T		intron	N/A	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.2463+4908A>T		intron	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.000146 AC: 22 AN: 150472 Hom.: 1 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000665

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.000481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000146 AC: 22 AN: 150588 Hom.: 1 Cov.: 26 AF XY: 0.000164 AC XY: 12 AN XY: 73358

African (AFR) AF: 0.00 AC: 0 AN: 40944

American (AMR) AF: 0.0000664 AC: 1 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.00105 AC: 5 AN: 4754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67792

Other (OTH) AF: 0.000476 AC: 1 AN: 2102

Alfa AF: 0.000353 Hom.: 1939

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.083
PhyloP100		-0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs640831; hg19: chr5-31459435;